Bile acid alterations associated with indolent course of inflammatory bowel disease.

BACKGROUND: The indolent course of treatment-naive patients with inflammatory bowel disease (IBD) is confirmed predictable based on clinical characteristics. Current evidences supported that bile acids (BAs) alteration might be promising biomarkers in the field of IBD. We aimed to analyze the alterations of BAs as the disease progresses and explore their predictive value for indolent course of IBD. METHODS: The indolent course of IBD was defined as a disease course without need for strict interventions throughout the entire follow-up. A targeted metabolomics method was used to detect the concentration of 27 BAs from serum sample in treatment-naive patients with IBD (Crohn's disease [CD], n = 27; ulcerative colitis [UC], n = 50). Patients with CD and UC were individually divided into two groups for further study according to the median time of indolent course. The overall BAs profile and the clinical value of BAs in predicting indolent course of IBD were identified between different groups. RESULTS: For CD, the levels of deoxycholic acid, glycodeoxycholic acid, taurodeoxycholic acid, glycolithocholic acid-3-sulfate disodium salt and iso-lithocholic acid were significantly increased in patients with indolent course > 18 M (p < 0.05). These five BAs owned 83.5% accuracy for predicting indolent course over 18 months in CD. For UC, the concentration of deoxycholic acid and glycodeoxycholic acid were significantly higher, while dehydrocholic acid were lower in patients with indolent course > 48 M (p < 0.05). These three BAs predicted indolent course over 48 months of 69.8% accuracy in UC. CONCLUSION: The specific BAs alterations might be potential biomarkers in predicting disease course of IBD patients.

Additive Engineering by Bifunctional Guanidine Sulfamate for Highly Efficient and Stable Perovskites Solar Cells.

High efficiency and good stability are the challenges for perovskite solar cells (PSCs) toward commercialization. However, the intrinsic high defect density and internal nonradiative recombination of perovskite (PVK) limit its development. In this work, a facile additive strategy is devised by introducing bifunctional guanidine sulfamate (GuaSM; CH6 N3 + , Gua+ ; H2 N-SO3 - , SM- ) into PVK. The size of Gua+ ion is suitable with Pb(BrI)2 cavity relatively, so it can participate in the formation of low-dimensional PVK when mixed with Pb(BrI)2 . The O and N atoms of SM- can coordinate with Pb2+ . The synergistic effect of the anions and cations effectively reduces the trap density and the recombination in PVK, so that it can improve the efficiency and stability of PSCs. At an optimal concentration of GuaSM (2 mol%), the PSC presents a champion power conversion efficiency of 21.66% and a remarkably improved stability and hysteresis. The results provide a novel strategy for highly efficient and stable PSCs by bifunctional additive.

Bone-Bound Bisphosphonates Inhibit Proliferation of Breast Cancer Cells.

Bisphosphonates are used in treating patients with breast cancer. In vitro studies have shown that bisphosphonates act directly on tumour cells, inhibiting cell proliferation and inducing apoptosis. In most such studies, drugs were added to culture media exposing cells to high bisphosphonate concentrations in solution. However, since bisphosphonates bind to bone hydroxyapatite with high affinity and remain bound for very long periods of time, these experimental systems are not an optimal model for the action of the drugs in vivo. The aim of this study was to determine whether bone-bound zoledronate has direct effects on adjacent breast cancer cells. Bone slices were pre-incubated with bisphosphonate solutions, washed, and seeded with cells of the breast cancer cell lines, MCF7 or MDA-MB-231. Proliferation was assessed by cell counts and thymidine incorporation for up to 72 h. Inhibition of the mevalonate pathway was tested by measuring the levels of unprenylated Rap1A, and apoptosis was examined by the presence of cleaved caspase-8 on western blots. The proliferation rate of breast cancer cells on zoledronate-treated bone was significantly lower compared to cells on control bone. Other bisphosphonates showed a similar inhibitory effect, with an order of potency similar to their clinical potencies. Unprenylated Rap1A accumulated in MCF7 cells on zoledronate-treated bone, suggesting zoledronate acted through the inhibition of the mevalonate pathway. Accumulation of cleaved caspase-8 in MDA-MB-231 cells on bisphosphonate-treated bone indicated increased apoptosis in the cells. In conclusion, bone-bound zoledronate inhibits breast cancer cell proliferation, an activity that may contribute to its clinical anti-tumour effects.

Lack of Evidence that Soluble Urate Directly Influences Bone Remodelling: A Laboratory and Clinical Study.

INTRODUCTION: Numerous observational studies have reported that serum urate concentration positively correlates with bone density and reduced risk of fractures. The aim of this study was to examine whether soluble urate directly influences bone remodelling. METHODS: In laboratory studies, the in vitro effects of soluble urate were examined in osteoclast, osteoblast and osteocyte assays at a range of urate concentrations consistent with those typically observed in humans (up to 0.70 mmol/L). The clinical relevance of the in vitro assay findings was assessed using serial procollagen-1 N-terminal propeptide (P1NP) and Month 12 bone density data from a randomised controlled trial of allopurinol dose escalation in people with gout. RESULTS: Addition of urate in the RAW264.7 cell osteoclastogenesis assay led to small increases in osteoclast formation (ANOVA p = 0.018), but no significant difference in bone resorption. No significant effects on osteoclast number or activity were observed in primary cell osteoclastogenesis or resorption assays. Addition of urate did not alter viability or function in MC3T3-E1 pre-osteoblast, primary human osteoblast, or MLO-Y4 osteocyte assays. In the clinical trial analysis, reducing serum urate over a 12 month period by allopurinol dose escalation did not lead to significant changes in P1NP or differences in bone mineral density. CONCLUSION: Addition of soluble urate at physiological concentrations does not influence bone remodelling in vitro. These data, together with clinical trial data showing no effect of urate-lowering on P1NP or bone density, do not support a direct role for urate in influencing bone remodelling.

Role of Marrow Adipocytes in Regulation of Energy Metabolism and Bone Homeostasis.

PURPOSE OF REVIEW: The goal of this review is to gain a better understanding of marrow adipocyte development, its regulation of energy, and its characterization responsible for bone homeostasis. RECENT FINDINGS: Despite major advances in uncovering the complex association of bone-fat in the marrow, the underlying basic biological process of adipose tissue development, as well as its interaction with bone homeostasis in pathophysiological conditions, is still not well understood. This review identifies many pro- and anti-osteogenic factors secreted by adipocytes to play a role in the manipulating the fate of mesenchymal stem cells as well as the osteoblastic activity during bone remodeling. It also addresses the function of adipose tissue capable of negative regulation of the hematopoietic microenvironment to influence the bone quantity and the nature of bone homeostasis.

Counter electrodes in dye-sensitized solar cells.

Dye-sensitized solar cells (DSSCs) are regarded as prospective solar cells for the next generation of photovoltaic technologies and have become research hotspots in the PV field. The counter electrode, as a crucial component of DSSCs, collects electrons from the external circuit and catalyzes the redox reduction in the electrolyte, which has a significant influence on the photovoltaic performance, long-term stability and cost of the devices. Solar cells, dye-sensitized solar cells, as well as the structure, principle, preparation and characterization of counter electrodes are mentioned in the introduction section. The next six sections discuss the counter electrodes based on transparency and flexibility, metals and alloys, carbon materials, conductive polymers, transition metal compounds, and hybrids, respectively. The special features and performance, advantages and disadvantages, preparation, characterization, mechanisms, important events and development histories of various counter electrodes are presented. In the eighth section, the development of counter electrodes is summarized with an outlook. This article panoramically reviews the counter electrodes in DSSCs, which is of great significance for enhancing the development levels of DSSCs and other photoelectrochemical devices.

Synthesis and in vitro bone cell activity of analogues of the cyclohexapeptide dianthin G.

The cyclohexapeptide natural product dianthin G promotes osteoblast (bone-forming cell) proliferation in vitro at nanomolar concentrations, and is therefore considered a promising candidate for the treatment of osteoporosis. An N(α)-methyl amide bond scan of dianthin G was performed to probe the effect of modifying amide bonds on osteoblast proliferation. In addition, to provide greater structural diversity, a series of dicarba dianthin G analogues was synthesised using ring closing metathesis. Dianthin G and one novel dicarba analogue increased the number of human osteoblasts and importantly they did not increase osteoclast (bone-resorbing cell) differentiation in bone marrow cells.

Poly(3-hexylthiophene)/perovskite Heterointerface by Spinodal Decomposition Enabling Efficient and Stable Perovskite Solar Cells.

The best research-cell efficiency of perovskite solar cells (PSCs) is comparable with that of mature silicon solar cells (SSCs); However, the industrial development of PSCs lags far behind SSCs. PSC is a multiphase and multicomponent system, whose consequent interfacial energy loss and carrier loss seriously affect the performance and stability of devices. Here, by using spinodal decomposition, a spontaneous solid phase segregation process, in situ introduces a poly(3-hexylthiophene)/perovskite (P3HT/PVK) heterointerface with interpenetrating structure in PSCs. The P3HT/PVK heterointerface tunes the energy alignment, thereby reducing the energy loss at the interface; The P3HT/PVK interpenetrating structure bridges a transport channel, thus decreasing the carrier loss at the interface. The simultaneous mitigation of energy and carrier losses by P3HT/PVK heterointerface enables n-i-p geometry device a power conversion efficiency of 24.53% (certified 23.94%) and excellent stability. These findings demonstrate an ingenious strategy to optimize the performance of PSCs by heterointerface via Spinodal decomposition.

A reversible redox strategy for SWCNT-based supercapacitors using a high-performance electrolyte.

In order to achieve pesudocapacitive performance of single-wall carbon nanotube (SWCNT) electrodes, a high-efficient and reversible redox strategy utilizing a redox-mediated electrolyte for SWCNT-based supercapacitors is reported. In this novel redox-mediated electrolyte, the single-electrode specific capacitance of the supercapacitor is heightened four times, reaching C=162.66 F g(-1) at 1 A g(-1). The quick charge-discharge ability of the supercapacitor is also enhanced, and the relaxation time is as low as 0.58 s. Furthermore, the supercapacitor shows an excellent cycling performance of 96.51 % retention after 4000 cycles. The remarkable results presented here illustrate that the redox strategy is a facile and straightforward approach to improve the performances of SWCNT electrodes.

Qualitative and quantitative analysis of volatile constituents from latrines.

More than 2.5 billion people defecate in the open. The increased commitment of private and public organizations to improving this situation is driving the research and development of new technologies for toilets and latrines. Although key technical aspects are considered by researchers when designing new technologies for developing countries, the basic aspect of offending malodors from human waste is often neglected. With the objective of contributing to technical solutions that are acceptable to global consumers, we investigated the chemical composition of latrine malodors sampled in Africa and India. Field latrines in four countries were evaluated olfactively and the odors qualitatively and quantitatively characterized with three analytical techniques. Sulfur compounds including H2S, methyl mercaptan, and dimethyl-mono-(di;tri) sulfide are important in sewage-like odors of pit latrines under anaerobic conditions. Under aerobic conditions, in Nairobi for example, paracresol and indole reached concentrations of 89 and 65 µg/g, respectively, which, along with short chain fatty acids such as butyric acid (13 mg/g) explained the strong rancid, manure and farm yard odor. This work represents the first qualitative and quantitative study of volatile compounds sampled from seven pit latrines in a variety of geographic, technical, and economic contexts in addition to three single stools from India and a pit latrine model system.

Long-chain triazolyl acids as inhibitors of osteoclastogenesis.

Saturated fatty acids (e.g., palmitic acid) are known to moderately inhibit the development of osteoclasts in vitro. In pursuit of more effective inhibitors of osteoclastogenesis we explored two new classes of palmitic acid analogues containing either an ether or triazolyl group at various positions along the chain. The compounds were evaluated for their ability to inhibit the formation of osteoclasts in primary mouse bone marrow cultures. The oxyacids were generally prepared by condensation of the appropriate alkyl halides and diols, followed by Jones oxidation. The triazolyl acids were prepared by copper-catalysed click chemistry between alkyl azides and acetylenic acids, or with the appropriately-protected azides and alkynes, followed by deprotection and oxidation. The oxyacids were little more effective than palmitic acid, but the triazolyl analogues were much more effective osteoclastogenesis inhibitors, especially when the triazole was distant from the acid unit.

Mucosa-Associated Oscillospira sp. Is Related to Intestinal Stricture and Post-Operative Disease Course in Crohn's Disease.

Intestinal stricture remains one of the most intractable complications in Crohn's disease (CD), and the involved mechanisms are poorly understood. Accumulating evidence suggests that the gut microbiota contributes to the pathogenesis of intestinal fibrosis. In this study, we investigated specific mucosa-associated microbiota related to intestinal strictures and their role in predicting postoperative disease course. Twenty CD patients who had undergone operative treatments were enrolled and followed up. Intestinal mucosa and full-thickness sections from stenotic and non-stenotic sites were sterilely collected. DNA extraction and bacterial 16s rRNA gene sequencing were conducted. Radiological and histological evaluations were performed to assess fibrosis. Microbial alpha diversity was significantly decreased in stenotic sites (p = 0.009). At the genus level, Lactobacillus, Oscillospira, Subdoligranulum, Hydrogenophaga, Clostridium and Allobaculum were decreased in stenotic segments (p < 0.1). The difference in Oscillospira sp. (stenotic vs. non-stenotic) was negatively correlated with the erythrocyte sedimentation rate (correlation coefficient (CC) -0.432, p = 0.057) and white blood cell count (CC -0.392, p = 0.087) and positively correlated with serum free fatty acids (CC 0.575, p < 0.05). This difference was negatively associated with intestinal fibrosis evaluated by imagological and histological methods (CC -0.511 and -0.653, p < 0.05). Furthermore, CD patients with a higher abundance of Oscillospira sp. in the residual intestine might experience longer remission periods (p < 0.05). The mucosa-associated microbiota varied between stenotic and non-stenotic sites in CD. Most notably, Oscillospira sp. was negatively correlated with intestinal fibrosis and postoperative disease course. It could be a promising biomarker to predict post-operative disease recurrence and a microbial-based therapeutic target.

Deregulated Expression of miR-483-3p Serves as a Diagnostic Biomarker in Severe Pneumonia Children with Respiratory Failure and Its Predictive Value for the Clinical Outcome of Patients.

Severe pneumonia in children is a group of inflammatory diseases of respiratory tract caused by pathogenic microorganisms. Increasing evidence suggested the crucial effects of microRNA on inflammatory diseases. This study aimed to reveal the expression and role of miR-483-3p in the serum of children with severe pneumonia, and to explore the effect of miR-483-3p on the biological function of lipopolysaccharide (LPS)-induced MRC-5 cells. MRC-5 cells were disposed with LPS to construct an in vitro pneumonia cell model. The relative expression level of miR-483-3p was measured by qRT-PCR. ROC curve was used to evaluate the diagnostic value of miR-483-3p in severe pneumonia. The Kaplan-Meier curve was performed to test the characteristics of survival distribution of different miRNA classifications. Cell viability and apoptosis were performed by CCK-8 assay and flow cytometry. IL-1ß, TNF-α, and IL-6 were detected by ELISA. Luciferase reporter gene assay and western blot analysis were performed to detect the interaction between miR-483-3p and IGF-1. The expression of serum miR-483-3p in severe pneumonia patients was higher than in controls. The AUC value of the ROC curve was 0.919, indicating that miR-483-3p had diagnostic value for severe pneumonia. The survival curve showed that patients with high expression of miR-483-3p had higher mortality. Cell viability and apoptosis assay showed that overexpression of miR-483-3p suppressed cell proliferation and promoted apoptosis. And upregulation of miR-483-3p promoted generation of inflammatory cytokines. Luciferase report gene assay and western blot assay both illustrated that IGF-1 might be the target gene of miR-483-3p. Serum miR-483-3p can be used as a biomarker for the diagnosis of severe pneumonia. High expression of miR-483-3p promoted the development of severe pneumonia.

Country-Specific Environmental Risks of Fragrance Encapsulates Used in Laundry Care Products.

Fragrance encapsulates (FEs) are designed to deliver fragrance components, notably in laundry care products. They are made of thermoset polymeric shells surrounding the fragrance content. These materials enter the environment mainly during laundry washing, but little is known about their distribution in and impact on the environment. The aim of the present study was to estimate the environmental concentrations of FE shells in freshwater, sediment, and soil compartments for 34 selected countries and to compare them with ecotoxicological effects. Probabilistic material flow analysis was used to estimate worst-case predicted environmental concentrations (PECs). The lowest freshwater PEC was predicted for Finland (0.00011 µg/L) and the highest for Belgium (0.13 µg/L). Accumulation of FE shells between 2010 and 2019 was considered for sediments and sludge-treated soils. The PECs in sediments ranged from 3.0 µg/kg (Finland) to 3400 µg/kg (Belgium). For sludge-treated soil, the concentration was estimated to be between 0 (Malta and Switzerland) and 3600 µg/kg (Vietnam). Ecotoxicological tests showed no effects for FE shells at any tested concentration (up to 2700 µg/L freshwater, 5400 µg/kg sediment, and 9100 µg/kg soil), thus not allowing derivation of a predicted-no-effect concentration (PNEC). Therefore, to characterize the environmental risks, the PEC values were compared with highest-observed-no-effect concentrations (HONECs) derived from ecotoxicological tests. The PEC/HONEC ratios were 9.3 × 10-6 , 0.13, and 0.04 for surface waters, sediments, and sludge-treated soils, respectively, which are much below 1, suggesting no environmental risk. Because the PEC values constitute an upper boundary (no fate considered) and the HONEC values represent a lower boundary (actual PNEC values based on NOECs will be higher), the current risk estimation can be considered a precautionary worst-case assessment. Environ Toxicol Chem 2022;41:905-916. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Phytochemistry: ibuprofen-like activity in extra-virgin olive oil.

Newly pressed extra-virgin olive oil contains oleocanthal--a compound whose pungency induces a strong stinging sensation in the throat, not unlike that caused by solutions of the non-steroidal anti-inflammatory drug ibuprofen. We show here that this similar perception seems to be an indicator of a shared pharmacological activity, with oleocanthal acting as a natural anti-inflammatory compound that has a potency and profile strikingly similar to that of ibuprofen. Although structurally dissimilar, both these molecules inhibit the same cyclooxygenase enzymes in the prostaglandin-biosynthesis pathway.

Hotspots, Frontiers, and Emerging Trends of Superabsorbent Polymer Research: A Comprehensive Review.

Superabsorbent polymer (SAP) is a kind of functional macromolecule with super-high water absorption and retention properties, which attracts extensive research and has wide application, especially in the areas of hygiene and agriculture. With reference to the Web of Science database, the SAP research literature from 2000 to 2019 is reviewed both quantitatively and qualitatively. By examining research hotspots, top research clusters, the most influential works, the representative frontier literature, and key emerging research trends, a visual panorama of the continuously and significantly increasing SAP research over the past 2 decades was presented, and issues behind the sharp increase in the literature were discovered. The findings are as follows. The top ten keywords/hotspots headed by hydrogel highlight the academic attention on SAP properties and composites. The top ten research themes headed by clay-based composites which boast the longest duration and the strongest impact have revealed the academic preference for application rather than theoretical study. Academically influential scholars and research studies have been acknowledged, and the Wu group was at the forefront of the research; however, more statistically significant works have been less detected in the last 10 years despite the sharper increase in publications. Hydrogel, internal curing, and aerogel are both current advances and future directions.

Factors affecting the mixed-layer concentrations of singlet oxygen in sunlit lakes.

The steady-state concentration of singlet oxygen within a lake ([1O2]SS) is an important parameter that can affect the environmental half-life of pollutants and environmental fate modelling. However, values of [1O2]SS are often determined for the near-surface of a lake, and these values typically do not represent the average over the epilimnia of lakes. In this work, the environmental and physical factors that have the largest impact on [1O2]SS within lake epilimnia were identified. It was found that the depth of the epilimnion has the largest impact on depth-averaged [1O2]SS, with a factor of 8.8 decrease in [1O2]SS when epilimnion depth increases from 2 m to 20 m. The next most important factors are the wavelength-dependent singlet oxygen quantum yield relationship and the latitude of the lake, causing variations in [1O2]SS by factors of 3.2 and 2.5 respectively, over ranges of representative values. For a set of representative parameters, the depth-averaged value of [1O2]SS within an average epilimnion depth of 9.0 m was found to be 5.8 × 10-16 M and the near-surface value of [1O2]SS was found to be 1.9 × 10-14 M. We recommend a range of 6 × 10-17 to 5 × 10-15 M as being more representative of [1O2]SS values within the epilimnia of lakes globally and potentially more useful for estimating pollutant lifetimes than those calculated using [1O2]SS values that correspond to near-surface, summer midday values. This work advances our understanding of [1O2]SS inter-lake variability in the environment, and provides estimates of [1O2]SS for practitioners and researchers to assess environmental half-lives of pollutants due to reaction with singlet oxygen.

Removal of humic acid and Cr(â ¥) from water using ZnO-30N-zeolite.

The mutual influence of humic acid and Cr(Ⅵ) on water purification using ZnO-30N-zeolite was investigated in the laboratory. The removal of humic acid by ZnO-30N-zeolite with both pollutants present reached 90% in 5 min. With humic acid alone, more than one day was required to reach the same level of removal. Synergy between humic acid and chromium was thus demonstrated in their removal process by ZnO-30N-zeolite. However, the presence of humic acid showed no obvious effect on the removal capacity of Cr(Ⅵ) by ZnO-30N-zeolite. X-ray photoelectron spectra showed that Cr(VI) was reduced to Cr(Ⅲ) in the process by both humic acid and ZnO-30N-zeolite. The kinetic mechanism of synergistic removal of humic acid and Cr(Ⅵ) by ZnO-30N-zeolite in binary pollutant system was also proposed.

The Clinical Features of FLAIR-Hyperintense Lesions in Anti-MOG Antibody Associated Cerebral Cortical Encephalitis with Seizures: Case Reports and Literature Review.

Background: The presence of fluid attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated cerebral cortical encephalitis with seizures (FLAMCES) was recently reported. However, the clinical characteristics and outcome of this rare clinico-radiographic syndrome remain unclear. Methods: The present study reported two new cases. In addition, cases in the literature were systematically reviewed to investigate the clinical symptoms, magnetic resonance imaging (MRI) abnormalities, treatments and prognosis for this rare clinico-radiographic syndrome. Results: A total of 21 cases were identified during a literature review, with a mean patient age at onset of 26.8 years. The primary clinicopathological characteristics included seizures (100%), headache (71.4%), fever (52.3%) and other cortical symptoms associated with the encephalitis location (61.9%). The common seizure types were focal to bilateral tonic-clonic seizures (28.6%) and unknown-onset tonic-clonic seizures (38.1%). The cortical abnormalities on MRI FLAIR imaging were commonly located in the frontal (58.8%), parietal (70.6%) and temporal (64.7%) lobes. In addition, pleocytosis in the cerebrospinal fluid was reported in the majority of the patients (95.2%). All patients received a treatment regimen of corticosteroids and 9 patients received anti-epileptic drugs. Clinical improvement was achieved in all patients; however, one-third of the patients reported relapse following recovery from cortical encephalitis. Conclusions: FLAMCES is a rare phenotype of MOG-associated disease. Thus, the wider recognition of this rare syndrome may enable timely diagnosis and the development of suitable treatment regimens.